Vasopressin receptor antagonists: Pharmacological tools and potential therapeutic agents

1 The present survey deals with the development and applications of non-peptidergic vasopressin receptor antagonists. 2 The existence of at least three vasopressin receptors (V1, V2 and V3 respectively) is firmly established. 3 V1-receptors play a relevant role in the regulation of vascular tone, whereas V2-receptors are known to mediate the antidiuretic activity of vasopressin at the level of the renal collecting ducts. The V3-receptor appears to be involved in the release of the adreno-corticotropic hormone. 4 Vasopressin receptor antagonists which are peptides have been known for several decades, more recently, both V1- and V2-receptor blockers which are non-peptidergic have been introduced, as well as agents with affinity for both V1- and V2-receptor subtypes. A survey of these non-peptidergic antagonists is presented here. Such compounds are useful as pharmacological tools, and they can also be thought of as therapeutic agents as therapeutic agents in cardiovascular and renal diseases. 5 Selective V1- and V2-receptor antagonists were used to study the interaction between vasopressin receptors and sympathetic neurones. Depending on the experimental model used this interaction can occur at either the pre- or postsynaptic sites. In both cases predominantly V1-receptors are involved. 6 A brief survey is given of the potential use of V-receptor antagonists in the drug therapy of syndrome of inappropriate antidiuretic hormone secretion and other water retaining disorders, congestive heart failure and certain forms of hypertension (in particular in the Negroid hypertensive patients). © 2006 Blackwell Publishing Ltd.